Assessing the Effects of Teriparatide Treatment on Bone Mineral Density, Bone Microarchitecture, and Bone Strength.

Background: To gain insight into how teriparatide affects various bone health parameters, we assessed the effects of teriparatide treatment with use of standard DXA (dual x-ray absorptiometry) technology and two newer technologies, high-resolution MRI (magnetic resonance imaging) and finite element analysis of quantitative CT (computed tomography) scans.

Methods: In this phase-4, open-label study, postmenopausal women with severe osteoporosis received 20 μg/day of teriparatide. Assessments included (1) changes in areal BMD (bone mineral density) (in g/cm) at the radius, spine, and hip on DXA, (2) changes in volumetric BMD (in mg/cm) at the spine and hip on quantitative CT scans, (3) changes in bone microarchitecture at the radius on high-resolution MRI, (4) estimated changes in spine and hip strength according to finite element analysis of quantitative CT scans, (5) changes in bone turnover markers in serum, and (6) safety.

Effects of low-dose estrogen replacement during childhood on pubertal development and gonadotropin concentrations in patients with Turner syndrome: results of a randomized, double-blind, placebo-controlled clinical trial.

Context: The optimal approach to estrogen replacement in girls with Turner syndrome has not been determined.

Objective: The aim of the study was to assess the effects of an individualized regimen of low-dose ethinyl estradiol (EE2) during childhood from as early as age 5, followed by a pubertal induction regimen starting after age 12 and escalating to full replacement over 4 years.

Design: This study was a prospective, randomized, double-blind, placebo-controlled clinical trial.

Fracture risk prediction: importance of age, BMD and spine fracture status.

Our purpose was to identify factors for a parsimonious fracture risk assessment model considering morphometric spine fracture status, femoral neck bone mineral density (BMD) and the World Health Organization (WHO) clinical risk factors. Using data from 2761 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, longitudinal cohort study of randomly selected community-dwelling men and women aged ⩾50 years, we previously reported that a logistic regression model considering age, BMD and spine fracture status provided as much predictive information as a model considering these factors plus the remaining WHO clinical risk factors. The current analysis assesses morphometric vertebral fracture and/or nonvertebral fragility fracture at 5 years using data from an additional 1964 CaMos subjects who have now completed 5 years of follow-up (total N=4725).

Hip and spine strength effects of adding versus switching to teriparatide in postmenopausal women with osteoporosis treated with prior alendronate or raloxifene.

Many postmenopausal women treated with teriparatide for osteoporosis have previously received antiresorptive therapy. In women treated with alendronate (ALN) or raloxifene (RLX), adding versus switching to teriparatide produced different responses in areal bone mineral density (aBMD) and biochemistry; the effects of these approaches on volumetric BMD (vBMD) and bone strength are unknown. In this study, postmenopausal women with osteoporosis receiving ALN 70 mg/week (n = 91) or RLX 60 mg/day (n = 77) for ≥18 months were randomly assigned to add or switch to teriparatide 20 µg/day.

SOME NEW FINITE DIFFERENCE METHODS FOR HELMHOLTZ EQUATIONS ON IRREGULAR DOMAINS OR WITH INTERFACES.

Solving a Helmholtz equation Δu + λu = f efficiently is a challenge for many applications. For example, the core part of many efficient solvers for the incompressible Navier-Stokes equations is to solve one or several Helmholtz equations. In this paper, two new finite difference methods are proposed for solving Helmholtz equations on irregular domains, or with interfaces.

Skeletal histomorphometry in subjects on teriparatide or zoledronic acid therapy (SHOTZ) study: a randomized controlled trial.

Context: Recent studies on the mechanism of action (MOA) of bone-active drugs have rekindled interest in how to present and interpret dynamic histomorphometric parameters of bone remodeling.

Objective: We compared the effects of an established anabolic agent, teriparatide (TPTD), with those of a prototypical antiresorptive agent, zoledronic acid (ZOL).

Design: This was a 12-month, randomized, double-blind, active-comparator controlled, cross-sectional biopsy study.

Changes in vitamin D metabolites during teriparatide treatment.

Parathyroid hormone (PTH) increases the conversion of 25-hydroxyvitamin D [25(OH)D] to 1,25 dihydroxyvitamin D [1,25(OH)(2)D]. The purpose of this study was to assess the changes in serum concentration of vitamin D metabolites 1,25 dihydroxyvitamin D [1,25(OH)(2)D] and 25-hydroxyvitamin D [25(OH)D] during teriparatide 20 μg/day (teriparatide) therapy in the double-blind Fracture Prevention Trial of postmenopausal women with osteoporosis and in the male study of men with osteoporosis. Patients were randomized to teriparatide or placebo and received daily supplements of calcium 1000 mg and vitamin D 400-1200 IU.

Changes observed in radionuclide bone scans during and after teriparatide treatment for osteoporosis.

Purpose: Visual changes on radionuclide bone scans have been reported with teriparatide treatment. To assess this, serial studies were evaluated and quantified in ten postmenopausal women with osteoporosis treated with teriparatide (20 μg/day subcutaneous) who had (99m)Tc-methylene diphosphonate (MDP) bone scans (baseline, 3 and 18 months, then after 6 months off therapy).

Methods: Women were injected with 600 MBq (99m)Tc-MDP, and diagnostic bone scan images were assessed at 3.

Femoral strength in osteoporotic women treated with teriparatide or alendronate.

To gain insight into the clinical effect of teriparatide and alendronate on the hip, we performed non-linear finite element analysis of quantitative computed tomography (QCT) scans from 48 women who had participated in a randomized, double-blind clinical trial comparing the effects of 18-month treatment of teriparatide 20 μg/d or alendronate 10mg/d. The QCT scans, obtained at baseline, 6, and 18 months, were analyzed for volumetric bone mineral density (BMD) of trabecular bone, the peripheral bone (defined as all the cortical bone plus any endosteal trabecular bone within 3 mm of the periosteal surface), and the integral bone (both trabecular and peripheral), and for overall femoral strength in response to a simulated sideways fall. At 18 months, we found in the women treated with teriparatide that trabecular volumetric BMD increased versus baseline (+4.

Nonparametric estimation of age-specific reference percentile curves with radial smoothing.

Reference percentile curves represent the covariate-dependent distribution of a quantitative measurement and are often used to summarize and monitor dynamic processes such as human growth. We propose a new nonparametric method based on a radial smoothing (RS) technique to estimate age-specific reference percentile curves assuming the underlying distribution is relatively close to normal. We compared the RS method with both the LMS and the generalized additive models for location, scale and shape (GAMLSS) methods using simulated data and found that our method has smaller estimation error than the two existing methods.

Comparative effects of teriparatide and strontium ranelate in the periosteum of iliac crest biopsies in postmenopausal women with osteoporosis.

The periosteum contains osteogenic cells that regulate the outer shape of bone and contribute to determine its cortical thickness, size and position. We assessed the effects of subcutaneous injections of teriparatide (TPTD, 20μg/day) or oral strontium ranelate (SrR, 2g/day) in postmenopausal women with osteoporosis on new bone formation activity at the periosteal and endosteal bone surfaces using dynamic histomorphometric measurements. Evaluable tetracycline-labeled transiliac crest bone biopsies were analyzed from 27 patients in the TPTD group, and 22 in the SrR group after six months of treatment.

Benefits and risks of raloxifene by vertebral fracture status.

Objective: Women without versus those with vertebral fracture may have different benefits and risks during raloxifene treatment. Our objective was to compare the effects of raloxifene to decrease risk for vertebral fracture and invasive breast cancer with its effect to increase risk for venous thromboembolism in postmenopausal women without or with baseline vertebral fracture.

Research Design And Methods: The Multiple Outcomes of Raloxifene Evaluation trial included postmenopausal women with osteoporosis randomized to placebo, raloxifene 60 mg/day, or raloxifene 120 mg/day for 4 years.

Mechanics of mesenchymal contribution to clefting force in branching morphogenesis.

Branching morphogenesis is ubiquitous and may involve several different mechanisms. Glandular morphogenesis is affected by growth, cell rearrangements, changes in the basal lamina, changes in the stromal ECM, changes in cell-cell and cell-ECM adhesions, mesenchymal contractility, and possibly other mechanisms. We have developed a 3D model of the mechanics of clefting, focusing in this paper solely on the potential role of mesenchyme-generated traction forces.